Phosphate-buffered saline extracts of corn have been found to be mitogenic for human peripheral blood lymphocytes. The present investigation was initiated to characterize the mitogenic components of corn as well as to identify the type of lymphocyte on which these mitogen act. In this project, lymphocytes from both human peripheral blood and mouse spleens were used. Only protein fractions of corn possessed mitogenic properties. These proteins consisted of a complex mixture of proteins most of which are mitogenic. Corn proteins are specific for the activation of mouse bone marrow-derived (B) lymphocytes as these proteins stimulated 1) spleen cells from athymic Nu/Nu mice and 2) only B lymphocytes obtained by fraction of whole spleen cells on a nylon-wool column. In humans, these proteins preferentially stimulated thymus-derived(T) lymphocytes, and this process was found to be macrophage-dependent.